Efficacy and Safety of 4 Weeks of Treatment With Inhaled BI 1744 CL in Patients With Asthma

Boehringer Ingelheim296 enrolled

Overview

The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL inhalation solution delivered by the Respimat® inhaler for four weeks in patients with asthma. The selection of the optimum dose(s) will be based on bronchodilator efficacy (how well it helps your breathing), safety evaluations and pharmacokinetic evaluations (the amount of the medication found in your blood).

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Enrollment

296

Conditions

Asthma

Interventions

BI 1744 CLDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions 2. Male or female patients, 18 years of age or older 3. Diagnosis of asthma (GINA) 4. Pre-bronchodilator FEV1 greater than or equal to 60% predicted and \<90% predicted (ECSC); 5. Increase in FEV1 greater than or equal to 12% and 200 ml 15 minutes after 400µg salbutamol (albuterol) at Visit 1 6. Patient must have been taking Inhaled Corticosteroids for at least 12 weeks prior to screening, and must have been receiving a stable low/moderate dose for at least 6 weeks prior to screening. 7. Patients must be able to perform technically acceptable pulmonary function tests and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol 8. Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI). Exclusion Criteria: 1. Patients with a smoking history of more than 10 pack years 2. Patients with any of the following conditions: a diagnosis of thyrotoxicosis, a diagnosis of paroxysmal tachycardia (\>100 beats per minute), a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms), a history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) 3. Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit (Visit 1), a diagnosis of clinically relevant cardiac arrhythmia, a history of cor pulmonale, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed), a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse 4. Patients who have undergone thoracotomy with pulmonary resection 5. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1) 6. Pregnant or nursing women 7. Women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least 2 years 8. Patients who have previously been randomized in this study or are currently participating in another study 9. Patients who are unable to comply with pulmonary medication restrictions prior to randomization

Locations (37)

Outcomes

Primary Outcomes

Trough FEV1 Response After 4 Weeks

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

Time frame: Baseline and 4 weeks

Secondary Outcomes

Weekly Mean Pre-dose Morning PEFR After 4 Weeks

Response was defined as change from baseline. Baseline peak expiratory flow response (PEFR) was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.

Time frame: Baseline and 4 weeks

Trough FEV1 Response After 1 Week

Time frame: Baseline and 1 week

Trough FEV1 Response After 2 Weeks

Time frame: Baseline and 2 weeks

Trough FVC Response After 1 Week

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

Data from ClinicalTrials.gov

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1222.6.064 Arthur F. Gelb Medical Corporation, Lakewood

Lakewood, California, United States

1222.6.062 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

1222.6.066 Allergy & Asthma Medical Group and Rsrch Ctr, APC

San Diego, California, United States

1222.6.069 Allergy Associates Medical Group

San Diego, California, United States

1222.6.068 National Jewish Medical Center

Denver, Colorado, United States

1222.6.073 Boehringer Ingelheim Investigational Site

Wheat Ridge, Colorado, United States

1222.6.067 Northeast Medical Research Associates, Inc

North Darthmouth, Massachusetts, United States

1222.6.061 Center for Human Genomics

Winston-Salem, North Carolina, United States

1222.6.072 Boehringer Ingelheim Investigational Site

Kileen, Texas, United States

1222.6.071 Pulmonary Consultants

Tacoma, Washington, United States

...and 27 more locations

Time frame: Baseline and 1 week

Trough FVC Response After 2 Weeks

Time frame: Baseline and 2 weeks

Trough FVC Response After 4 Weeks

Time frame: Baseline and 4 weeks

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4

Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Day 1

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 4

Peak FEV1 (0-3h) Response At Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1

Peak FEV1 (0-3h) Response After 1 Week

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week

Peak FEV1 (0-3h) Response After 2 Weeks

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

Peak FEV1 (0-3h) Response After 4 Weeks

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks

Peak FVC (0-3h) Response At Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 weeks

Peak FVC (0-3h) Response After 1 Week

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 weeks

Peak FVC (0-3h) Response After 2 Weeks

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

Peak FVC (0-3h) Response After 4 Weeks

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Time frame: 1 hour (h) prior to dose on first day of randomized treatment (baseline) and 1h, 3h, 6h, 9h, 12h relative to dose at Week 4

Weekly Mean Evening PEFR After 4 Weeks

Response was defined as change from baseline. Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.

Time frame: Baseline and 4 weeks

PEFR Variability After 4 Weeks

PEFR variability represents the absolute difference between the highest morning PEFR value and the highest evening PEFR value of 1 day, divided by the arithmetic mean of these 2 PEFR values and expressed as a percent, weekly means.

Time frame: 4 weeks

Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks

Weekly mean number of occasions of rescue therapy used per day (prn salbutamol \[albuterol\]) as assessed by the e-Diary (e-Diary incorporated in AM2+).

Time frame: 4 weeks

Area Under Curve From 0 to 3 Hours (AUC0-3)

AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3

Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration

Maximum Concentration (Cmax)

Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.

Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration

Time From Dosing to the Maximum Concentration (Tmax)

tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.

Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration

Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)

AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3 at steady state.